Controlled delivery of glial cell line-derived neurotrophic factor enhances motor nerve regeneration / 中国医师杂志

ABSTRACT

Objective To determine the effect of a motor-specific neurotrophic factor,glial-derived neurotrophic factor (GDNF) on motor nerve regeneration.Methods We used a nerve conduit filled with a fibrin-based delivery system that provided controlled release of GDNF during nerve regeneration.The motor branch of the rat femoral nerve was used to assess motor nerve regeneration across a 5-mm gap.Four experimental groups (n =5) were evaluated.These included GDNF with the fibrin-based delivery system (GDNFDS group),fibrin alone(fibrin group),empty conduit (negative control group),and nerve isograft (positive control group).Nerves were harvested at 5 weeks for analysis by histomorphometry and electron microscopy.Results At 5 mm distal to the conduit or isografts,the GDNF-DS group was not significantly different from the nerve isograft group in the following histomorphometric measures:total nerve fibers,percentage of neural tissue,and nerve density.The number of nerve fibers (respectively1 744 ± 274,1 481 ± 288)and the percentage of nerve tissue [(14.2 ± 3.9) ％,(11.0 ± 2.2) ％] in theisograft group and the GDNFDS group were significantly higher than that in the fibrin group and the empty conduit group [(respectively538 ± 93,535 ± 96) and the percentage of nerve tissue respectively(4.3 ± 1.6) ％,(3.7 ± 0.9) ％].There were no differences in fiber width among all groups.By electron microscopy,the GDNF-DS and isograft groups also demonstrated more organized nerve architecture than the fibrin alone and empty conduit groups.Conclusions The delivery of GDNF from the fibrin-based delivery system promotes motor nerve regeneration at a level similar to an isograft in the femoral motor nerve model.This study gives insight into the potential beneficial role of GDNF in the treatment of motor nerve injuries.